Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan; Department of Biotechnology and Genetic Engineering, Faculty of Science, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Biotechnol Adv. 2024 Dec;77:108456. doi: 10.1016/j.biotechadv.2024.108456. Epub 2024 Sep 24.
Heparin, a highly sulfated glycosaminoglycan, is considered an indispensable anticoagulant with diverse therapeutic applications and has been a mainstay in medical practice for nearly a century. Its potential extends beyond anticoagulation, showing promise in treating inflammation, cancer, and infectious diseases such as COVID-19. However, its current sourcing from animal tissues poses challenges due to variable structures and adulterations, impacting treatment efficacy and safety. Recent advancements in metabolic engineering and synthetic biology offer alternatives through bioengineered heparin production, albeit with challenges such as controlling molecular weight and sulfonation patterns. This review offers comprehensive insight into recent advancements, encompassing: (i) the metabolic engineering strategies in prokaryotic systems for heparin production; (ii) strides made in the development of bioengineered heparin; and (iii) groundbreaking approaches driving production enhancements in eukaryotic systems. Additionally, it explores the potential of recombinant Chinese hamster ovary cells in heparin synthesis, discussing recent progress, challenges, and future prospects, thereby opening up new avenues in biomedical research.
肝素是一种高度硫酸化的糖胺聚糖，被认为是一种不可或缺的抗凝剂，具有多种治疗应用，在医学实践中已有近一个世纪的历史。它的潜在用途不仅限于抗凝，在治疗炎症、癌症和传染病（如 COVID-19）方面也显示出前景。然而，由于其结构和掺杂物的可变性，目前从动物组织中提取肝素存在挑战，这会影响治疗效果和安全性。代谢工程和合成生物学的最新进展为生物工程生产肝素提供了替代方案，尽管存在控制分子量和硫酸化模式等挑战。本文综述了最近的进展，包括：（i）在原核系统中用于肝素生产的代谢工程策略；（ii）在生物工程肝素开发方面取得的进展；和（iii）推动真核系统生产增强的开创性方法。此外，它还探讨了重组中国仓鼠卵巢细胞在肝素合成中的潜力，讨论了最近的进展、挑战和未来前景，从而为生物医学研究开辟了新途径。
